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Primary Care Update


Metabolic syndrome: 5 risk factors guide therapy

Easy-to-use clinical values tell when to intervene.

Vol. 4, No. 4 / April 2005

At what point do the five risk factors that predict type 2 diabetes and cardiovascular disease (CVD) signal metabolic syndrome? When and how often should psychiatrists check for metabolic abnormalities? How can you manage metabolic problems caused by a psychotropic that controls the patient’s psychiatric symptoms?

This article answers those questions by addressing:

  • clinical guidelines for diagnosing metabolic syndrome
  • suggested intervals for monitoring at-risk patients
  • strategies for managing metabolic abnormalities with lifestyle changes or medication.

CASE REPORT: 'FAT' AND FRUSTRATED

Ms. S, age 37, has had bipolar disorder for 10 years. She has tried numerous medications including mood stabilizers, antidepressants, and atypical antipsychotics. The combination of quetiapine, 200 mg bid, and lithium, 300 mg bid, has controlled her symptoms for the past 6 months.

Her weight has increased 40 lbs over the past decade; much of her weight gain has occurred since the birth of her two children, ages 4 and 6. At 5 feet, 3 inches and 170 lbs, she is frustrated over her weight gain, especially on the eve of her 20-year high school reunion. She is convinced that her medications have prevented weight loss.

Her waist, measured at the umbilicus, is 37 inches. Her body mass index (BMI) is 30—indicating clinical obesity—and her blood pressure is in the high normal range (134/80 mm Hg). She has not had gestational diabetes and has not seen a medical doctor since her last pregnancy, but her father has type 2 diabetes and hypertension. She drinks wine occasionally at social events and does not smoke.

The psychiatrist orders a fasting lipid panel and fasting glucose test to further assess her risk of heart disease. Total cholesterol and low-density lipoprotein (LDL) cholesterol are normal. Triglycerides are 125 mg/dL (normal) and her high-density lipoprotein (HDL) is 45 mg/dL—5 mg/dL below normal for a woman her age. Fasting glucose is 86 mg/dL (normal).

The psychiatrist schedules a visit the following month to assess her cardiac and diabetic risk and to discuss weight-loss interventions.

Discussion. In a busy clinical setting, the psychiatrist must accurately gauge Ms. S’ metabolic risk and devise a management strategy. Do her weight and low HDL suggest metabolic syndrome? Is she overeating or making unhealthy dietary choices, or are her psychotropics causing weight gain? Would switching psychotropics lead to bipolar relapse?

IMPLICATIONS OF METABOLIC SYNDROME

Patients with metabolic syndrome are at increased risk for:

  • type 2 diabetes1
  • CVD2
  • increased mortality from CVD and all causes.3

In a prospective study that followed 1,209 Finnish men over an average 11.4 years,4 men with metabolic syndrome were more likely than those with no metabolic problems to die from coronary heart disease, CVD, and any cause after adjustment for conventional cardiovascular risk factors. No one in either group had a baseline illness, suggesting that metabolic syndrome increases the risk of CVD or death regardless of whether underlying illness is present.

DEFINING METABOLIC SYNDROME

Metabolic syndrome is not a disease but a constellation of risk factors that provides a definable point of intervention before onset of type 2 diabetes or CVD.

According to the National Cholesterol Education Program—Adult Treatment Panel III (NCEP-ATP III), presence of three of these five criteria suggest metabolic syndrome:

  • abdominal obesity
  • insulin resistance
  • high blood pressure
  • elevated triglycerides
  • below-normal HDL.

This definition offers a starting point for measuring risk factors in clinical practice and provides a definable target and parameters to avoid (Table 1).5 The guideline is also easy to follow: Waist circumference and blood pressure can be measured within seconds; blood glucose, HDL, and triglycerides can easily be measured before breakfast, after the patient has fasted for at least 6 hours.

Table 1

5 defined risk factors* for metabolic syndrome

Risk factor

Clinically significant level

Abdominal obesity

Men

Waist circumference >40 in (102 cm)

Women

Waist circumference >35 in (88 cm)

Blood pressure

Systolic

>130 mm Hg

Diastolic

>85 mm Hg

HDL count

Men

<40 mg/dL (<1.04 mmol/L)

Women

<50 mg/dL (<1.30 mmol/L)

Fasting glucose

Men, women

>110 mg/dL (>6.11 mmol/L)

Triglycerides

Men, women

>150 mg/dL (>1.70 mmol/L)

* If 3 risk factors are present, suspect metabolic syndrome

HDL: high-density lipoprotein cholesterol

Source: Adapted from reference 5.

MONITORING FREQUENCY

Although no empirical studies have addressed monitoring frequency for metabolic risk factors, several guidelines provide preliminary recommendations. Table 2 summarizes suggested intervals for monitoring weight, lipids, glucose, and waist circumference for patients taking atypical antipsychotics, based on recommendations from the 2004 American Diabetes Association (ADA) and American Psychiatric Association (APA) consensus development conference.6

Because atypicals are associated with serious metabolic risks, screen patients taking these agents for metabolic abnormalities at baseline and at regular intervals. Most guidelines recommend measuring blood pressure, BMI, waist circumference, fasting serum lipids (total, LDL, HDL, and triglycerides) and fasting glucose before starting or switching to an atypical and again 12 weeks later. Established risk for metabolic disturbances or dramatic metabolic changes (such as weight gain ≥7%, waist circumference ≥35 inches in women and ≥40 inches in men, or fasting blood sugars >110 mg/dL) demand more-frequent monitoring (ie, monitor high-risk patients quarterly).

Table 2

Suggested monitoring intervals for patients taking atypical antipsychotics*

 

Baseline

4 weeks

8 weeks

12 weeks

Quarterly

Annually

Every 5 years

Personal/family history

X

 

 

 

 

X

 

Weight (BMI)

X

X

X

X

X

 

 

Waist circumference

X

 

 

 

 

X

 

Blood pressure

X

 

 

X

 

X

 

Fasting plasma glucose

X

 

 

X

 

X

 

Fasting lipid profile

X

 

 

X

 

 

X

*Clinical status may warrant more-frequent assessments

BMI: Body mass index

Source: Reference 6.

MANAGING METABOLIC PROBLEMS

Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:

  • weight management, weight control education, and promoting regular exercise and a healthy diet
  • switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
  • working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.

Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.

Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.7 Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.7

Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.

Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,2 triglycerides,17 blood pressure,18 and hyperglycemia.19

In one prospective study,20 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.

Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:

  • 43% had lower triglycerides than at baseline
  • 16% had higher HDL cholesterol
  • 38% had lower blood pressure
  • 9% had improved fasting glucose
  • 28% reduced their waist circumference.

Table 3

Interventions for specific metabolic complications

Metabolic complication

Nondrug interventions8

Medications

Abdominal obesity

Encourage weight loss

Sibutramine*

Increase physical activity

Appetite suppressant

Orlistat*

Lipase inhibitor

Hypertriglyceridemia

Encourage weight loss

Fibrates9*

Increase physical activity

Reduce fasting and postprandial triglycerides 20% to 50%

Increase low-glycemic-index food intake

Shift small dense LDL to large buoyant particles

Reduce total carbohydrate intake

Increase HDL particles 10% to 35%

Increase consumption of omega-3 fatty acids

Nicotinic acid10

Limit alcohol consumption

Reduces triglycerides 20% to 50%

Statins11

Reduce fasting and postprandial triglycerides 7% to 30%

Reduce LDL particles

Increase HDL particles

Reduce major coronary vascular events

Low HDL

Encourage weight loss

Nicotinic acid*

Increase physical activity

Increases HDL particles 15% to 35%

Stop smoking

Fibrates9

Increase monounsaturated fat intake

See above

Statins11

See above

Hypertension

Encourage weight loss

ACE inhibitors*

Increase physical activity

May slow progression to diabetes12

Reduce saturated fat intake

Decrease CVD events13

Reduce sodium intake

Delay progression of microalbuminuria13

Limit alcohol consumption

Angiotensin receptor blockers

May improve dyslipidemia associated with metabolic syndrome14

Delay progression of microalbuminuria13

Hyperglycemia

Encourage weight loss

Metformin,* thiazolidinediones

Increase physical activity

Slow progression to diabetes in persons with insulin resistance15,16 (metformin less effective than lifestyle changes)15

Reduce total carbohydrates

* Suggested first-line therapy.

For patients with BMI 30 kg/m2

ACE: Angiotensin-converting enzyme

CVD: Cardiovascular disease

HDL: High-density lipoprotein cholesterol

LDL: Low-density lipoprotein cholesterol

Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.

By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.21

In a prospective 12-month trial,22 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.22

Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).

Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.

Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).6

Table 4

Atypical antipsychotics and their propensity for causing metabolic abnormalities

Drug

Weight gain

Hyperglycemia

Dyslipidemia

Clozapine

High

High

High

Olanzapine

High

High

High

Risperidone

Medium

Medium

Low

Quetiapine

Medium

Medium

High

Aripiprazole

Low

Low

Low

Ziprasidone

Low

Low

Low

Source: Reference 6

Targeted pharmacotherapy. Wait another 3 to 6 months to see if the medication change and weight loss/exercise interventions reduce metabolic risk factors. If they don’t, work with the patient’s primary care physician to manage hypertension, dyslipidemia, and obesity (Table 3).

Although no agents are approved for treating metabolic syndrome per se, medications targeted at individual symptoms are becoming the standard of care. Controlling blood pressure, HDL, and LDL in patients with metabolic syndrome can reduce risk for coronary heart disease by >50%.25 Insulin-sensitizing agents and metformin in combination with lifestyle changes or used alone have been shown to delay onset of type 2 diabetes (Table 3).

CASE CONTINUED: 10 LBS IN 10 WEEKS

At her follow-up visit, Ms. S and her psychiatrist discuss her increased risk for diabetes and cardiovascular disease. She meets criteria for metabolic syndrome (low HDL, elevated blood pressure, and increased waist circumference).

Ms. S agrees to try a formal diet program with set menus, along with group support at her local community center. She also commits to walking 30 minutes three to four times a week with a target heart rate of 100 beats per minute. Although both quetiapine and lithium carry considerable risk of weight gain, she and her psychiatrist decide to wait at least 3 months before considering a medication change, as she is stable on this combination.

Ms. S schedules a follow-up visit with her primary care physician to ensure that she sticks to her weight loss and exercise programs. In the interim, the primary care physician and psychiatrist agree that her goal will be to lose 10 lbs over 10 weeks.

Related resources

  • National Alliance for the Mentally Ill. Hearts and Minds Program, a booklet and program geared toward raising awareness regarding diabetes, diet, exercise, and smoking. Download at www.nami.org.
  • Centers for Disease Control and Prevention: Body mass index formula for adults. www.cdc.gov/nccdphp/dnpa/bmi/bmi-adult-formula.htm.
  • National Heart, Lung and Blood Institute body mass index calculator. www.nhlbisupport.com/bmi/bmicalc.htm.
  • Keck PE Jr, Buse JB, Dagago-Jack S, et al. Managing metabolic concerns in patients with severe mental illness. A special report. Postgraduate Med 2003;1-92.

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